ESPE Abstracts

Background: Woodhouse-Sakati syndrome (WSS) is an extremely rare autosomal recessive multisystem disease. Ectodermal system findings, such as alopecia and changes in facial skin, endocrinological problems including hypogonadism, hypothyroidism, diabetes mellitus (DM), and decreased levels of insulin-like growth factor I (IGF-I), neurological disorders such as hearing loss and progressive extrapyramidal involvement are the components of this syndrome. The syndrome is caused by homozygous or compound heterozygous mutations in DCAF17, and has been implicated in the development of both male and female gonads, thus resulting in hypogonadism. This gene encodes a nuclear transmembrane protein that associates with cullin 4A/damaged DNA binding protein 1 ubiquitin ligase complex. Alopecia and loss of hearing are generally present before puberty. Puberty is delayed in all cases, and primary amenorrhea is typically present in girls. Hypothyroidism and DM may be added to the manifestation after puberty, and neurological disorders in later decades. Here we describe a two novel homozygous DCAF17 mutations in 2 consanguineous Palestinian families presenting with primary amenorrhea.

Clinical Data: The 2 Palestinian females, presented with absence of spontaneous puberty, primary amenorrhea and hypergonadotropic hypogonadism (LH: 30.5 & 31.2, FSH: 75 & 31.2 respectively), Karyotype was 46, XX and pelvic MRI detected a small uterus but no ovaries in both affected patients. They did not develop alopecia, endocrinological and neurological disorders till now.

Molecular Data: next generation sequencing revealed a novel c.G395C, p.R132P mutation in the DCAF17 gene, both parents were heterozygous.

Conclusion: The two novel R132P mutations in DCAF17 gene causes hypergonadotropic hypogonadism and primary amenorrhea in 2 Palestinian families. The predicted change may compromise protein function which is currently studied. To our knowledge, this is the first description of this disease in a Palestinian family with molecular confirmation, allowing accurate genetic counseling, early diagnosis of affected kindreds & early therapeutic interventions. Paving the way for genetic testing of hypogonadism cases in Palestine.